PROJECT SUMMARY/ABSTRACT The overall goal of this application is to establish a thematic, multidisciplinary Center for Musculoskeletal Disease Research at the University of Arkansas for Medical Sciences (UAMS) via the COBRE mechanism. This will be a self-sustaining research center focused on identifying the molecular causes of diseases and conditions that negatively impact the musculoskeletal system or interact with this system as part of their disease process. Successfully establishing this COBRE will spur the development of new and effective therapies for a broad range of conditions, including osteoporosis, osteoarthritis, aberrant skeletal development, osteomyelitis, multiple myeloma, and cancer metastases to the bone. A key to the success of this Center will be the development of new independent investigators who are committed to team-based musculoskeletal research. To develop and operate this Center, the Administrative Core will establish the scientific and administrative infrastructure necessary to meet the needs of musculoskeletal researchers at UAMS and affiliated institutions and will oversee all organizational and budgetary aspects of Center development and function (Specific Aim 1). The Administrative Core will also implement a faculty development plan that will mentor four junior investigators to the point of independence, as measured by obtaining R01-level funding, and beyond (Specific Aim 2). The Administrative Core will support the growth of the Center by recruiting and promoting the development of new junior investigators to replace those that achieve independence via a pilot project program, the targeted recruitment of new investigators, and by effective Center evaluation (Specific Aim 3). These goals will be accomplished under the leadership of the Center Director who, with the support of experienced mentors and an Internal and External Advisory Committee, will guide four Project Leaders focused on musculoskeletal research to independence. The Administrative Core will also oversee the operation of three Research Cores providing state-of-the-art services to create new genetic models (Core B), perform specialized skeletal tissue analysis (Core C), and perform bioinformatic analyses of large molecular datasets (Core D). The overall success of this strategy will be gauged by achieving the following milestones within the first five years of Center funding: 1) three or more of the Project Leaders will successfully compete for NIH or federal R01-level research grant support to graduate to independent investigator status; 2) two to four new Project Leaders (and Mentors) will be selected and join the Center; 3) Project Leaders and other Center members will publish between 20 and 30 peer-reviewed publications; and 4) graduated Project Leaders and other members of the Center will be in the process of developing, or will have submitted, a center-level grant application, such as a P01 or P30.